The pathogenic Neisseria species are capable of utilizing transferrin as their sole source of iron. A neisserial transferrin receptor has been identified and its characteristics defined; however, the biochemical identities of proteins which are required for transferrin receptor function have not yet been determined. We The ability of many human pathogens to cause infection is dependent in part on their ability to acquire iron from their host. Unlike the members of the family Enterobacteriaceae, the pathogenic Neisseria species do not produce and secrete soluble siderophores to compete with host iron-binding proteins such as transferrin (Tf) and lactoferrin (Lf), but instead can acquire iron directly from these proteins (32, 33). Utilization requires direct contact between Tf and the cell membrane (1,30,53), which implies the presence of specific receptors for these iron-binding proteins. Recent evidence suggests that other human pathogens such as Haemophilus influenzae and Bordetella pertussis also possess specific receptors for Tf (43,48).Tf receptor function has been characterized in the pathogenic Neisseria species (8,27,50,58). Tf utilization and binding is iron repressible (27,50,53,60)

Pathogenic Neisseria species have been shown to scavenge iron from transferrin (Ti)

Neisseria gonorrhoeae is a common sexually transmitted pathogen that significantly impacts female fertility, neonatal health, and transmission of HIV worldwide. N. gonorrhoeae usually causes localized inflammation of the urethra and cervix by inducing production of IL-1␤ and other inflammatory cytokines. Several NLR (nucleotide-binding domain, leucine-rich repeat) proteins are implicated in the formation of pro-IL-1␤-processing complexes called inflammasomes in response to pathogens. We demonstrate that NLRP3 (cryopyrin, NALP3) is the primary NLR required for IL-1␤/IL-18 secretion in response to N. gonorrhoeae in monocytes. We also show that N. gonorrhoeae infection promotes NLRP3-dependent monocytic cell death via pyronecrosis, a recently described pathway with morphological features of necrosis, including release of the strong inflammatory mediator HMBG1. Additionally, N. gonorrhoeae activates the cysteine protease cathepsin B as measured by the breakdown of a cathepsin B substrate. Inhibition of cathepsin B shows that this protease is an apical controlling step in the downstream activities of NLRP3 including IL-1␤ production, pyronecrosis, and HMGB1 release. Nonpathogenic Neisseria strains (Neisseria cinerea and Neisseria flavescens) do not activate NLRP3 as robustly as N. gonorrhoeae. Conditioned medium from N. gonorrhoeae contains factors capable of initiating the NLRP3-mediated signaling events. Isolated N. gonorrhoeae lipooligosaccharide, a known virulence factor from this bacterium that is elaborated from the bacterium in the form of outer membrane blebs, activates both NLRP3-induced IL-1␤ secretion and pyronecrosis. Our findings indicate that activation of NLRP3-mediated inflammatory response pathways is an important venue associated with host response and pathogenesis of N.

The mainstay of diagnosis for Treponema pallidum infections is based on nontreponemal and treponemal serologic tests. Many new diagnostic methods for syphilis have been developed, using specific treponemal antigens and novel formats, including rapid point-of-care tests, enzyme immunoassays, and chemiluminescence assays. Although most of these newer tests are not yet cleared for use in the United States by the Food and Drug Administration, their performance and ease of automation have promoted their application for syphilis screening. Both sensitive and specific, new screening tests detect antitreponemal IgM and IgG antibodies by use of wild-type or recombinant T. pallidum antigens. However, these tests cannot distinguish between recent and remote or treated versus untreated infections. In addition, the screening tests require confirmation with nontreponemal tests. This use of treponemal tests for screening and nontreponemal serologic tests as confirmatory tests is a reversal of long-held practice. Clinicians need to understand the science behind these tests to use them properly in syphilis management.